Genotypes of the Mannan‐Binding Lectin Gene and Susceptibility to Visceral Leishmaniasis and Clinical Complications

Alonso, Diego Peres; Ferreira, Afonso F. B.; Ribolla, Paulo Eduardo Martins; Santos, Isabel Kinney Ferreira de Miranda; Cruz, Maria do Socorro Pires e; Carvalho, Fernando Aécio de Amorim; Abatepaulo, Antônio Roberto Rodrigues; Costa, Dorcas Lamounier; Werneck, Guilherme Loureiro; Farias, Teresinha J C; Soares, Maria José dos Santos; Costa, Carlos Henrique Nery

doi:10.1086/512683

Cited by 58 publications

(65 citation statements)

References 35 publications

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“…Epistaxis was the sole exception, possibly a result of the symptom's lack of specificity; in addition to edema and jaundice, it has been identified to be a strong risk factor for death in patients with visceral leishmaniasis. 3,39 Altogether, these observations suggest that disease-induced malnutrition is the main factor contributing to parasite replication, which secondarily may lead to systemic inflammation, depending upon virulence factors and genetically driven host response [40][41][42][43] Therefore, the present data suggest that the association of higher parasitemia with malnutrition and with death may be caused by a nutrition-dependent immunosuppression, leading both to higher parasite burden and to disease severity. However, in opposition to our findings, a previous study 21 found higher bone marrow parasite burden in patients with better prognosis and higher mortality in those with a low parasite load observed by microscopy.…”

Section: Discussionmentioning

confidence: 57%

Bone Marrow Parasite Burden among Patients with New World Kala-Azar is Associated with Disease Severity

Silva¹,

Zacarias

Figueirêdo

et al. 2014

The American Society of Tropical Medicine and Hygiene

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Abstract. Kala-azar or visceral leishmaniasis, found mostly throughout the Indian Subcontinent, East Africa, and Brazil, kills 20,000-40,000 persons annually. The agents, Leishmania donovani and Leishmania infantum, are obligatory intracellular protozoa of mononuclear phagocytes found principally in the spleen and bone marrow. Protracted fever, anemia, wasting, hepatosplenomegaly, hemorrhages, and bacterial co-infections are typical features. One hundred and twenty-two (122) in-hospital patients were studied to verify if higher bone marrow parasite load estimated by quantitative polymerase chain reaction is associated with severe disease. The estimated median parasite load was 5.0 parasites/ 10 6 human nucleated cells. It is much higher in deceased than among survivors (median 75.0 versus 4.2). Patients who lost more weight had a higher parasite burden, as well as patients with epistaxis, abdominal pain, edema, and jaundice. This study suggests that higher parasite load is influenced by wasting, which may lead to more severe disease.

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Section: Discussionmentioning

confidence: 57%

Bone Marrow Parasite Burden among Patients with New World Kala-Azar is Associated with Disease Severity

Silva¹,

Zacarias

Figueirêdo

et al. 2014

The American Society of Tropical Medicine and Hygiene

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“…Therefore, the absence of parasite actions or products that would harm the host cells or tissues is one more indication that the systemic pathogenicity of VL is dependent on the host response. Although inflammatory tests were not evaluated in this study, inflammation is an ordinary feature of VL, as indicated by increases in erythrocyte sedimentation rate and acute phase proteins [24][25][26] . Moreover, the proinflammatory cytokines interferon-γ, TNF and IL-6 and the chemokine IL-8 are elevated in VL as part of a broad and sustained innate response 27,32,33 .…”

Section: Discussionmentioning

confidence: 99%

Is severe visceral leishmaniasis a systemic inflammatory response syndrome? A case control study

Costa

Werneck

Costa

et al. 2010

Rev. Soc. Bras. Med. Trop.

119

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Introduction: The objective of the study is to identify the main risk factors for death by New World visceral leishmaniasis and establish a coherent pathogenic substrate of severe disease based on clinical findings. Methods: Seventy-six deceased inpatients and 320 successfully treated inpatients with VL were studied in a case control study. Results: Bacterial infection and bleeding were mutually exclusive events leading to death. Five risk factors were unique for death by bacterial infection (malnutrition, pulmonary rales, severe anemia, severe absolute neutropenia and higher neutrophil count), while another six were unique for death by bleeding (jaundice, severe relative neutropenia, severe thrombocytopenia, liver injury, kidney failure, higher bone marrow parasite load). Bacterial infection, bleeding, severe anemia, diarrhea, dyspnea, edema, jaundice and bone marrow parasite load were the main syndromes of visceral leishmaniasis among successfully treated patients. Conclusions: The data support the idea that bacterial infections are due to immune paralysis. Broad organ and system involvement is plausibly due to the high production of proinflammatory cytokines, whose actions fit well with visceral leishmaniasis. The syndromes and causative mediators are typical of a slowly developing systemic inflammatory response syndrome. Keywords: Visceral leishmaniasis. Kala-azar. Severe inflammatory response syndrome. AIDS. Bleeding. RESUMO Introdução: O objetivo do estudo foi identificar os principais fatores de risco para morte na leishmaniose visceral do Novo Mundo e estabelecer um substrato patogênico baseado nos achados clínicos coerente para doença grave. Métodos: Em um estudo caso-controle, foram estudados 76 pacientes internados que faleceram e 320 pacientes internados tratados com sucesso. Resultados: Infecção bacteriana e sangramento foram eventos que levaram à morte, mutuamente exclusivos. Cinco fatores de risco foram únicos para morte por infecção bacteriana (desnutrição, estertores pulmonares, anemia grave, neutropenia absoluta grave e número de leucócitos aumentados), enquanto outros seis foram exclusivos para morte por sangramento (icterícia, neutropenia relativa grave, trombocitopenia grave, lesão hepática, insuficiência renal, maior carga de parasitas na medula óssea). Entre os pacientes tratados com sucesso, as principais síndromes de leishmaniose visceral foram infecções bacterianas, sangramento, anemia grave, diarreia, dispneia, edema, icterícia e carga de parasitas na medula óssea. Conclusões: Os dados apoiam a ideia de que as infecções bacterianas são secundárias a imunoparalisia. O amplo envolvimento de órgãos e sistemas é de forma plausível devido a elevada produção de citocinas pró-inflamatórias, cujas ações se encaixam com a leishmaniose visceral. As síndromes e os mediadores causais são típicos da síndrome de resposta inflamatória sistêmica, desenrolando-se lentamente. Palavras-chaves: Leishmaniose visceral. Calazar. Síndrome da resposta inflamatória sistêmica. AIDS. Sangramento.

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“…Third, although from the public health perspective the control of symptomatic cases is a priority, the non-use of markers for infection prevents the demarcation of transmission foci because more infections occur than cases of the disease [35][36][37][38] and the evolution from asymptomatic infected status to symptomatic status is mediated by genetic and nutritional factors. [39][40][41] Finally, as mentioned, this study is based on secondary data available in SINAN. Thus, although VL is a serious disease subject to mandatory reporting (and the treatment of which is only provided by government health services), the available data are based on passive case detection, and one cannot rule out the possibility of case underreporting.…”

Section: 13mentioning

confidence: 99%

Identification of Risk Areas for Visceral Leishmaniasis in Teresina, Piaui State, Brazil

Almeida¹,

Medronho²,

Werneck³

2011

The American Society of Tropical Medicine and Hygiene

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This study used spatial analysis to identify areas at greatest risk of visceral leishmaniasis (VL) in the urban area of Teresina, Brazil during 2001–2006. The results from kernel ratios showed that peripheral census tracts were the most heavily affected. Local spatial analysis showed that in the beginning of the study period local clusters of high incidence of VL were mostly located in the southern and northeastern parts of the city, but in subsequent years those clusters also appeared in the northern region of the city, suggesting that the pattern of VL is not static, and the disease may occasionally spread to other areas of the municipality. We also observed a spatial correlation between VL rates and all socioeconomic and demographic indicators evaluated (P < 0.01). The concentration of interventions in high-risk areas could be an effective strategy to control the disease in the urban setting.

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Genotypes of the Mannan‐Binding Lectin Gene and Susceptibility to Visceral Leishmaniasis and Clinical Complications

Abstract: Genotypes of the MBL2 gene predict the risk for developing VL and clinical complications in infections with L. chagasi.

Cited by 58 publications

References 35 publications

Bone Marrow Parasite Burden among Patients with New World Kala-Azar is Associated with Disease Severity

Bone Marrow Parasite Burden among Patients with New World Kala-Azar is Associated with Disease Severity

Is severe visceral leishmaniasis a systemic inflammatory response syndrome? A case control study

Identification of Risk Areas for Visceral Leishmaniasis in Teresina, Piaui State, Brazil

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